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Citicoline, a compound found in several natural products, shows promise for improving mental function, according to research conducted by scientists at the University of Utah's Brain Institute.
In an industry-funded study, a team led by Deborah Yurgelun-Todd found that middle-aged women demonstrated improved ability to focus after two weeks on a daily regimen of the supplement.
"Our findings suggest that citicoline may mitigate the cognitive decline associated with normal aging and improve attentional deficits associated with over-stimulation of the brain," said Yurgelun-Todd, a professor of psychiatry who directs the Cognitive Neuroimaging Laboratory at the Brain Institute. She is also a consultant for Kyowa Hakko, a Japanese firm that manufactures citicoline under the brand name Cognizin, used as an ingredient in supplements and a new energy drink called Nawgan (pronounced "noggin").
The findings have not yet been submitted for publication in a peer-reviewed journal, but were presented this month at the annual meeting of the New Clinical Drug Evaluation Unit, organized by the American Society of Clinical Psychopharmacology and the National Institutes of Health. The study earned lead author Eric McGlade, a research fellow at the Brain Institute, a New Investigator award. Authors include the Brain Institute's Allison Locatelli and four scientists associated with Kyowa Hakko, which funded the study.
While the researchers have close ties to the manufacturer of the substance they tested, they note that the study was scientifically rigorous and that the relationship was disclosed to the U.'s conflict-of-interest committee.
Citicoline is a nucleotide that can cross the blood-brain barrier and is crucial to cellular metabolism. It occurs naturally in almonds and other foods but in amounts too tiny for humans to gain much benefit, even with large consumptions, Yurgelun-Todd said. Kyowa Hakko is a leading producer, with its Cognizin appearing as the active ingredient in several supplements. A one-month supply of one product, at two 250-milligram capsules a day, costs $35.95.
The U. recruited Yurgelun-Todd from Harvard two years ago along with her husband, Perry Renshaw, a biomedical researcher who studies addiction. In conjunction with the Utah Science Technology and Research initiative, or USTAR, the pair now explore ways to use brain scans as a diagnostic tool. As researchers at the Harvard-affiliated McLean Hospital, they studied the effects of citicoline on appetite suppression and memory and its ability to treat addiction. Using functional magnetic resonance imaging and magnetic resonance spectroscopy — scanning technologies that illustrate brain activity in real time — they found the substance showed notable potential for dampening desire for food and methamphetamine and improving energy levels in the brain's frontal lobe, the seat of our "executive functions." Those studies were co-funded by the National Institutes of Health and Kyowa Hakko.
Citicoline is manufactured by other firms under the names Ceraxon, NeurAxon, Somazin and other brands. Yurgelun-Todd uses Cognizin in her research because she contends Kyowa Hakko has the best quality control, so researchers can be sure they are administering consistent dosages. The company has retained the couple as consultants since their days at McLean.
Such relationships are not uncommon at research universities, according to Steven Roy, an outreach executive with USTAR. Officials say they are appropriate as long as they are disclosed to the university's conflict-of-interest committee if a researcher's stake in the sponsoring firms or consulting fee exceeds $10,000.
An increasing share of the U.'s research funding comes from private industry, last year reaching $42 million, or roughly 10 percent of total funding. Kyowa Hakko has spent $230 million on research in the United States, according to its website.
"We have a strong natural-products sector in our state. It seemed like a good idea to connect the dots to see if there was a fit," Roy said. Natural products producers are going to face more regulation, and that means the value of those products will have to be proved in the laboratory, he said. So contracting with reputable academic researchers only makes sense.
"They get the results, but they don't know what the results are going to be," Roy said.
The latest study was double-blind and placebo-controlled to meet some of the highest standards in biomedical research. Yurgelun-Todd's team recruited 60 Salt Lake-area women between the ages of 40 and 60 and randomly assigned them to three groups for the four-week duration of the study. They were instructed to take a capsule once a day, but none of the women knew whether they were taking an actual supplement. Neither did the researchers who evaluated the women at the beginning of the study and again after two and four weeks.
One group's dose was 250 milligrams of Cognizin, another took 500 milligrams and the third took the placebo, a capsule with no active ingredient. The goal of the trial was to determine how low a dose was needed to get a beneficial effect and how quickly the effect would occur.
At two-week intervals, the women underwent neuropsychiatric evaluations by answering questions and taking what's called a continuous performance test, or CPT, a standard cognition measure.
After two weeks, the women taking citicoline demonstrated greater ability to focus attention than those taking the placebo, and they self-reported a greater sense of well-being. Yurgelun-Todd did not observe much difference in performance between the two dosage levels.
"They showed significantly better ability to produce correct responses on the attention task, presumably due to improved cognition," Yurgelun-Todd said. "This was a really robust, rigorous study for showing the effect, which is unusual for natural products."
Yurgelun-Todd chose to study middle-aged women to capture those experiencing menopause, which affects cognition. She plans to continue the study on adolescents.